The structures of biological macromolecules determined by X-ray crystallography provide an unparalleled level of detailed information and make possible the design of therapeutics aimed at treating human illnesses. This proposal seeks to acquire an X-ray generator and associated optics for NIH-supported investigators at the University of California, San Diego (UCSD). The one and only X-ray generator for macromolecular crystallography at UCSD is an antiquated Rigaku FR-C that was purchased in 1990. The Rigaku FR-C requires a great deal of maintenance, and worryingly is no longer supported by Rigaku. This makes parts either impossible to get or very expensive. As more and more parts break down on the FR-C, we are finding it increasingly difficult to continue operation with this generator. To solve this problem, we propose to acquire a Rigaku MicroMaxTM 007 HF and its associated optics (VariMaxTM). (The current optics will not support the microfocus beam of the MicroMaxTM-007 HF.) A home X-ray generator is essential in two ways. First, it provides a means for screening crystals (including cryopreservative conditions) for diffraction prior to data collection at a synchrotron X-ray source. Without such screening, data collection at the synchrotron would need to be carried out in blind and wasteful fashion. Second, a home source enables data collection and structure determination to be carried out at home for crystals that diffract well, freeing up valuable synchrotron time for challenging projects. The proposed equipment will replace the current X-ray generator in the Macromolecular Crystallography Facility, which has an experienced staff engineer who manages daily operations, and will be administered by the existing Macromolecular Crystallography Facility Committee. UCSD has a long tradition of X-ray crystallography, and this commitment continues today. This commitment is evidenced by financial support for personnel to manage the equipment from the Department of Chemistry & Biochemistry and the Skaggs School of Pharmacy and Pharmaceutical Sciences. The Macromolecular Crystallography Facility has also offered to commit funds to pay for the costs of removal and disposal of the current X-ray generator. The long-term support of the equipment will be derived from user fees (i.e., on a recharge basis). UCSD has a substantial number of X-ray crystallographers whose research efforts depend on regular access to a home source of X-rays. In short, the proposed instrumentation is crucial to the campus-wide success of X-ray crystallography at UCSD. PUBLIC HEALTH RELEVANCE: The structures of biological macromolecules determined by X-ray crystallography provide an unparalleled detailed level of information and make possible the design of therapeutics aimed at treating human illnesses. This proposal seeks to obtain an X-ray generator and associated optics to enable such structure determination by investigators at the University of California, San Diego. This equipment will enable a large group of biomedical scientists at this campus to gain fundamental knowledge relevant to human diseases, and to apply this knowledge to therapeutics.